Anxiety disorders are a debilitating form of mental illness that affect many people and carry a high societal and economic burden. A central feature of these disorders is the excessive anticipation of potential adverse outcomes. Considerable work in the candidate's and others' labs has identified multiple brain areas recruited during the anticipation of aversive events. The primary research objectives of this application are to probe these areas for abnormalities during anticipation in anxiety disorder patients and to examine the impact of uncertainty and uncontrollability, which figure prominently in anxiety. The planned research will also assess functional associations and white matter connections among the brain networks identified. In service of that, training in functional and structural connectivity methods is the major focus of the career development plan. These rapidly developing areas examining connectivity are an obvious next step for the candidate's research program and career development and will be crucial in his efforts to continue contributing to our developing knowledge base about brain function in anxiety. The environment is ideal for the pursuit of these research and career development objectives, with outstanding facilities, collaborators, and resources as well as a high degree of support from both the Department of Psychiatry and the Waisman Center. The proposed research will examine anticipatory function in generalized anxiety disorder and social anxiety disorder using a picture paradigm designed and developed in the candidate's laboratory over the past 7 years. The high levels of comorbidity with depression for these two anxiety disorders will be systematically investigated by including patients with major depressive disorder. The discovery of neural abnormalities in anticipatory processes should add to the body of work already being used in developing new clinical tools for directly targeting specific brain regions in anxiety and depression, such as transcranial magnetic stimulation, epidural electrocortical stimulation, and deep brain stimulation. Psychotherapy clients may benefit from greater focus of intervention strategies on anticipatory processes relevant to their symptoms. Research findings from the proposed project might have implications for determining which individuals would be likely to benefit from a particular treatment, building on recent findings by the candidate and his colleagues that greater anticipatory activity in the anterior cingulate predicts better response to an 8-week medication trial.